Our long term goals are to determine the receptors and mechanisms involved in cell interactions with the extracellular matrix (ECM) and other cells and how these recaptors function cooperatively in differentiation and morphogenic processes. We have defined three structurally and functionally related ECM receptors (ECMRs), II, VI and I, of 140 kDa each that mediate mesenchymal cell adhesion to collagen, fibronectin and collagen/fibronectin/laminin, respectively, We have also defined a fourth ECMR of 90 kDa, that binds to collagen, termed collagen receptor III (CRIII), that is expressed in most nucleated cells. CRIII interacts with a proteoglycan (GAG200) and is homologous to the Hermes-1 and Mel 14 antigens, mediators of lymphocyteendothelial cell adhesion. Thus, CRIII may mediate cell-cell adhesion in many cell populations as well as interact with the ECM. The ECMR are also expressed by epithelial cells and often ECM ligand suggesting additional possible functions for the ECMRs. This proposal will utilize biochemical and immunological techniques to evaluate; 1. THE FUNCTIONAL ROLE OF CRIII IN MEDIATING INTERCELLULAR ADHESION IN MULTIPLE CELL POPULATIONS. (A) Development of assays to examine the role of CRIII in cell-cell adhesion. (B) Identification of a ligand, possible GAG200 or collagen, for CRIII involved in cell-cell adhesion. II.THE FUNCTIONAL ROLE OF ECMRS IN LOCALIZING EPITHELIAL AND OTHER CELLS TO TISSUE DOMAINS (A) Localization of ECMRs in normal and malignant tissue in relation to ECM components. (B) Development of assays to evaluate the role of ECM-ECMB interactions in epithelium. (C) The role of ECM-ECMR interactions in expression of epithelial cell characteristics (polarity, migration, differentiation).